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A Network Pharmacology Approach for Exploring the Mechanisms of Panax notoginseng Saponins in Ischaemic Stroke.

ABSTRACT:

Background

Panax notoginseng saponins (PNS) have been deemed effective herb compounds for treating ischaemic stroke (IS) and improving the quality of life of IS patients. This study aimed to investigate the underlying mechanisms of PNS in the treatment of IS based on network pharmacology.

Methods

PNS were identified from the Traditional Chinese Medicine System Pharmacology (TCMSP) database, and their possible targets were predicted using the PharmMapper database. IS-related targets were identified from the GeneCards database, OMIM database, and DisGeNET database. A herb-compound-target-disease network was constructed using Cytoscape, and protein-protein interaction (PPI) networks were established with STRING. GO enrichment and KEGG pathway analysis were performed using DAVID. The binding of the compounds and key targets was validated by molecular docking studies using AutoDock Vina. The neuroprotective effect of TFCJ was substantiated in terms of oxidative stress (superoxide dismutase, glutathione peroxidase, catalase, and malondialdehyde) and the levels of IGF1/PI3K/Akt pathway proteins.

Results

A total of 375 PNS targets and 5111 IS-related targets were identified. Among these targets, 241 were common to PNS, and IS network analysis showed that MAPK1, AKT1, PIK3R1, SRC, MAPK8, EGFR, IGF1, HRAS, RHOA, and HSP90AA1 are key targets of PNS against IS. Furthermore, GO and KEGG enrichment analysis indicated that PNS probably exert therapeutic effects against IS by regulating many pathways, such as the Ras, oestrogen, FoxO, prolactin, Rap1, PI3K-Akt, insulin, PPAR, and thyroid hormone signalling pathways. Molecular docking studies further corroborated the experimental results.The network pharmacology results were further verified by molecular docking and in vivo experiments.

Conclusions

The ameliorative effects of PNS against IS were predicted to be associated with the regulation of the IGF1-PI3K-Akt signalling pathway. Ginsenoside Re and ginsenoside Rb1 may play an important role in the treatment of IS.

SUBMITTER: Wang C

PROVIDER: S-EPMC8382556 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:Panax notoginseng (Burk) F. H. Chen, as traditional Chinese medicine, has a long history of high clinical value, such as anti-inflammatory, anti-oxidation, inhibition of platelet aggregation, regulation of blood glucose and blood pressure, inhibition of neuronal apoptosis, and neuronal protection, and its main ingredients are Panax notoginseng saponins (PNS). Currently, Panax notoginseng (Burk) F. H. Chen may improve mental function, have anti-insomnia and anti-depression effects, alleviate anxiety, and decrease neural network excitation. However, the underlying effects and the mechanisms of Panax notoginseng (Burk) F. H. Chen and its containing chemical constituents (PNS) on these depression-related or anxiety-related diseases has not been completely established. This review summarized the antidepressant or anxiolytic effects and mechanisms of PNS and analyzed network targets of antidepressant or anxiolytic actions with network pharmacology tools to provide directions and references for further pharmacological studies and new ideas for clinical treatment of nervous system diseases and drug studies and development. The review showed PNS and its components may exert these effects through regulating neurotransmitter mechanism (5-HT, DA, NE), modulation of the gamma-amino butyric acid (GABA) neurotransmission, glutamatergic system, hypo-thalamus-pituitary-adrenal (HPA) axis, brain-derived neurotrophic factor (BDNF), and its intracellular signaling pathways in the central nervous system; and produce neuronal protection by anti-inflammatory, anti-oxidation, or inhibition of neuronal apoptosis, or platelet aggregation and its intracellular signaling pathways. Network target analysis indicated PNS and its components also may have anti-inflammatory and anti-apoptotic effects, which leads to the preservation of brain nerves, and regulate the activity and secretion of nerve cells, exerting anti-depression and anxiolytic effects, which may provide new directions for further in-depth researches of related mechanisms.